title: Designing drug trials for Alzheimer's disease: what we have learned from the release of the phase III antibody trials: a report from the EU/US/CTAD Task Force.
abstract: An international task force of investigators from academia, industry, nonprofit foundations, and regulatory agencies met in Monte Carlo, Monaco, on October 31, 2012, to review lessons learned from the recent bapineuzumab and solanezumab trials, and to incorporate insights gained from these trials into future clinical studies. Although there is broad consensus that Alzheimer's disease (AD) should be treated during its earliest stages, the concept of secondary prevention has evolved to be described more accurately as treatment of preclinical, presymptomatic, or early AD. There continues to be a strong emphasis on biomarkers and a need for new biomarkers; however, there has also been a realization, based on completed trials, that the most reliable indicator of clinical efficacy across the entire spectrum of disease from asymptomatic to AD dementia is likely a measure of cognition. The task force made many recommendations that should improve the likelihood of success in future trials, including larger phase 2 or combined phase 2/phase 3 studies, clear evidence of target engagement in the central nervous system, evidence of downstream effects on biomarkers before initiating phase 3 studies, consideration of adaptive and targeted trial designs, and use of sensitive measures of cognition as the most robust indicator of treatment benefit.
authors.affiliation: UMR1027 Inserm, Toulouse, France. vellas.bruno@gmail.com
authors.forename: Bruno
authors.initials: B
authors.lastname: Vellas
authors.forename: Maria C
authors.initials: MC
authors.lastname: Carrillo
authors.forename: Cristina
authors.initials: C
authors.lastname: Sampaio
authors.forename: H Robert
authors.initials: HR
authors.lastname: Brashear
authors.forename: Eric
authors.initials: E
authors.lastname: Siemers
authors.forename: Harald
authors.initials: H
authors.lastname: Hampel
authors.forename: Lon S
authors.initials: LS
authors.lastname: Schneider
authors.forename: Michael
authors.initials: M
authors.lastname: Weiner
authors.forename: Rachelle
authors.initials: R
authors.lastname: Doody
authors.forename: Zaven
authors.initials: Z
authors.lastname: Khachaturian
authors.forename: Jesse
authors.initials: J
authors.lastname: Cedarbaum
authors.forename: Michael
authors.initials: M
authors.lastname: Grundman
authors.forename: Karl
authors.initials: K
authors.lastname: Broich
authors.forename: Ezio
authors.initials: E
authors.lastname: Giacobini
authors.forename: Bruno
authors.initials: B
authors.lastname: Dubois
authors.forename: Reisa
authors.initials: R
authors.lastname: Sperling
authors.forename: Gordon K
authors.initials: GK
authors.lastname: Wilcock
authors.forename: Nick
authors.initials: N
authors.lastname: Fox
authors.forename: Philip
authors.initials: P
authors.lastname: Scheltens
authors.forename: Jacques
authors.initials: J
authors.lastname: Touchon
authors.forename: Suzanne
authors.initials: S
authors.lastname: Hendrix
authors.forename: Sandrine
authors.initials: S
authors.lastname: Andrieu
authors.forename: Paul
authors.initials: P
authors.lastname: Aisen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control*; D016229:Amyloid beta-Peptides / Q000032:analysis; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D001057:Apolipoproteins E / Q000032:analysis / Q000235:genetics; D001284:Atrophy / Q000209:etiology; D015415:Biomarkers; D001921:Brain / Q000473:pathology; D001923:Brain Chemistry; D001929:Brain Edema / Q000209:etiology; D017322:Clinical Trials, Phase II as Topic / Q000706:statistics & numerical data; D017326:Clinical Trials, Phase III as Topic / Q000379:methods*; D060825:Cognitive Dysfunction / Q000188:drug therapy; D018450:Disease Progression; D023381:Endpoint Determination / Q000379:methods; D006801:Humans; D015337:Multicenter Studies as Topic / Q000379:methods*; D059906:Neuroimaging; D018697:Nootropic Agents / Q000627:therapeutic use*; D018579:Patient Selection; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D017211:Treatment Failure
chemical_list: D016229:Amyloid beta-Peptides; D061067:Antibodies, Monoclonal, Humanized; D001057:Apolipoproteins E; D015415:Biomarkers; D018697:Nootropic Agents; C550616:solanezumab; C545458:bapineuzumab